A Bioassay for the Cytotoxicity of Gemcitabine Using the Marine Ciliate Euplotes vannus
- 2 Downloads
This study investigated the cytotoxicity of gemcitabine using the marine ciliate Euplotes vannus as the test organism. The median lethal concentrations (LC50 values) were determined using acute toxicity tests within an exposure time of 30 min with 0, 6, 12, 24, and 48 mg mL−1 gemcitabine. The median inhibition effect (IC50 value) on the growth of the ciliate cells was examined using chronic toxicity tests within 5 days (120 h) after exposure for 30 min with 0, 0.7, 3.5, 7, and 14 mg mL−1 gemcitabine. The 30-min LC50 value was 10.66mg mL−1. The LC50 values decreased with increasing exposure times and well fitted to the toxicity curve equation LC50 = 10.93 + 28.4e−0.19t (R2 =0.93; P < 0.05, t=exposure time). The IC50 value for growth rates was 7.05 mg mL−1, and the inhibition effect on growth rates well fitted to the model equation r%= 0.8681e−0.0782Cgem (r% means growth rate with inhibition by gemcitabine, Cgem means concentrations of gemcitabine, R2 =0.99 and P< 0.05). The LC50 values of a wide range of gemcitabine concentrations could therefore be predicted for any given exposure time. These results suggest that the clinical dose of gemcitabine (20mg mL−1) was higher than the 30-min LC50 value, which was almost the same as the 6-min LC50 value (19.88 mg mL−1) for E. vannus cells. The results also demonstrate that E. vannus can be used as a robust test organism for bioassays of chemotherapeutic drugs during short exposure periods.
Key wordsbioassay cytotoxicity Euplotes vannus gemcitabine toxicology
Unable to display preview. Download preview PDF.
This work was supported by the National Natural Science Foundation of China (Nos. 31672308 and 40206021).
- Bearden, A. P., Sinks, G. D., and Schultz, T. W., 1999. Acclimation to sublethal exposures to a model nonpolar narcotic: Population growth kinetics and membrane lipid alterations i. Tetrahymena pyriformis. Aquatic Toxicology, 46: 11–21.Google Scholar
- Chen, Z., and Song, W., 2002. Phylogenetic postions of Aspi-disca steini and Euplotes vannus within the order Euplotida (Hypotrichia: Ciliophora) inferred from complete small sub-unit ribosomal RNA gene sequences. Acta Protozoologica, 41: 1–9.Google Scholar
- Dive, D., and Leclerc, H., 1975. Standardized test method using protozoa for measuring water pollutant toxicity. Progress in Water Technology, 7: 67–72.Google Scholar
- Fuma, S., Ishii, N., Takeda, H., Miyamoto, K., Yanagisawa, K., Ichimasa, Y., Saito, M., Kawabata, Z., and Polikarpov, G., 2003. Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation. Journal of Environmental Radioactivity, 67: 1–14.CrossRefGoogle Scholar
- Girling, A. E., Pascoe, D., Janssen, C. R., Peither, A., Wenzel, A., Schafer, H., Neumeier, B., Mitchell, G. C., Taylor, E. J., Maund, S. J., Lay, J. P., Juttner, I., Crossland, N. O., Stephenson, R. R., and Persoone, G., 2000. Development of methods for evaluating toxicity to freshwater ecosystems. Ecotoxicology and Environemental Safety, 45: 148–176.CrossRefGoogle Scholar
- Gray, J. S., and Ventilla, R. J., 1973. Growth rates of sediment living marine protozoa as a toxicity indicator for heavy metals. AMBIO, 2: 118–121.Google Scholar
- Herllung-Larsen, P., Assaad, F., Pankratova, S. B., Saietz, L., and Skovgaard, L. T., 2000. Effects of pluronic F-68 on Tetrahy-mena cells: Protection against chemical and physical stress and prolongation of survival under toxic conditions. Biotechnology, 76: 185–195.Google Scholar
- Hong, Y., Tan, Y., Meng, Y., Yang, H., Zhang, Y., Warren, A., Li, J., and Lin, X., 2017. Evaluation of biomarkers for ecotoxicity assessment by dose-response dynamic models: Effects of ni-trofurazone on antioxidant enzymes in the model ciliated protozoa. Euplotes vannus. Ecotoxicology and Environmental Safety, 144: 552–559.CrossRefGoogle Scholar
- Li, J., Zhou, L., Lin, X., Yi, Z., and Al-Rasheid, K. A. S., 2014. Characterizing dose-reponse of catalase to nitrofurazone exposure in model ciliated protozoa. Euplotes vannus for ecoto-xicity assessment: Enzyme activity and mRNA expression. Ecotoxicology and Environemental Safety, 100: 294–302.CrossRefGoogle Scholar
- Pishvaian, M. J., and Brody, J. R., 2017. Therapeutic implications of molecular subtyping for pancreatic cancer. Oncology (Williston Park, N.Y.), 31: 159–166, 168.Google Scholar
- Rachel, A., 2009. Cancer Chemotherapy. Wiley-Blackwell, Oxford, 369pp.Google Scholar
- Zhang, X. W., Ma, Y. X., Sun, Y., Cao, Y. B., Li, Q., and Xu, C. A., 2017. Gemcitabine in combination with a second cytotoxic agent in the first-line treatment of locally advanced or metastatic pancreatic cancer: A systematic review and meta-analysis. Targeted Oncology, 12 (3): 309–321, DOI: 10.1007/s11523-017-0486-5.CrossRefGoogle Scholar